Tagatose-1,6-diphosphate

Besides FDPA, three other aldolases using DHAP as the donor are known each aldolase generates a new C3-C4 bond with a different stereochemistry u-erythro for fuculose-l-phosphate aldolase, i.-threo for rhamnulose 1-phosphate aldolase, and D-erythro for tagatose 1,6-diphosphate aldolase [7]. These aldolases accept a great variety of electrophilic substrates, which has been widely exploited in synthesis of sugar analogues [8,9]. 

Thomas, T. D. 1975. Tagatose-1,6-diphosphate activation of lactate dehydrogenase from Streptococcus cremoris. Biochem. Biophys. Res. Commun. 63, 1035-1042. Thomas, T. D. 1976A. Activator specificity of pyruvate kinase from lactic streptococci. J. BacterioL 125, 1240-1242. 

Two new stereocenters are established in the DHAP-dependent aldolases-cata-lyzed carbon-carbon bond formation. Consequently four different stereoisomers can be formed (Scheme 5.23). Enantioselective aldolases that catalyze the formation of just one of each of the stereoisomers are available fructose 1,6-diphosphate aldolase (FDP A), rhamnulose 1-phosphate aldolase (Rha 1-PA), L-fucu-lose 1-phosphate aldolase (Fuc 1-PA) and tagatose 1,6-diphosphate aldolase (TDP A). In particular the FDP A, that catalyzes the formation of the D-threo stereochemistry, has been employed in many syntheses. One such FDP A that... 

In vivo, six known DHAP-dependent aldolases are known to catalyze the reversible enanotioselective aldol addition of dihydroxyacetone phosphate to an acceptor aldehyde. The group is comprised of fructose 1,6-diphosphate (FDP) aldolase (EC 4.1.2.13), L-fuculose 1-phosphate (Fuc 1-P) aldolase (EC 4.1.2.17), tagatose 1,6-diphosphate (TDP) aldolase (EC 4.1.2.2), ketotetrose phosphate aldolase (EC 4.1.2.2), L-rhamnulose 1-phosphate (Rha 1-P) aldolase (EC 4.1.2.19), and phospho-5-keto-2-deoxygluconate aldolase (EC 4.1.2.29). The in vivo catalyzed reactions of this group are shown in Scheme 5.3. 

A one-pot procedure has been proposed for the conversion of dihydroxyacetone and PEP into D-tagatose-1,6-diphosphate 6 (Scheme 13.12). The reaction mixture contains glycerolkinase, pyruvate kinase, triose phosphate isomerase, and a D-tagatose 1,6-diphosphate aldolase [27]. 

D. L. Bissett and R. L. Anderson, Isolation and properties of a class I D-ketohexose-1,6-diphosphate aldolase that catalyses the cleavage of D-tagatose-1,6-diphosphate, J. Biol. Chem., 255 (1980) 8750-8755. 

In the really enzymemimetic process, the aldol reaction of (S)-2 with aldehydes, one obtains as depicted in scheme 3 polyhydroxylated ketones of the anti-(3S,4S) -configuration, hitherto difficult to prepare by either chemical or enzymatic methods (D-tagatose-1,6-diphosphate aldolase) [9]. Whereas excellent diastereomeric excess could be obtained after flash-chromatography (de > 95%), the maximum enantiomeric excess of so far up to 82% has yet to be optimized [16]. 

In continuation of earlier work with over-expressed enzymes from E. coli (see Vol.25, Chapter 7, ref.44), D-tagatose 1,6-diphosphate has been synthesized from dihydroxyacetone by use of a combination of several enzymes including a newly isolated tagatose 1,6-bisphosphate aldolase. An efficient synthesis of D-fructose 1,6-diphosphate by use of four enzymes in a one pot operation has been described. D-[1- C] Fructose 6-phosphate has been prepared from C-enriched formaldehyde and D-ribose 5-phosphate by a formaldehyde fixing enzyme system from Methylomonas aminofaciens, and various C-substituted D-fructose phosphates have been obtained by enzymic methods from C-substituted pyruvate or L-alanine. ... 

A new route to monosaccharides employing catalysed asymmetric aldol condensation has been illustrated by the preparation of L-fucose from crotonaldehyde and ketene silyl acetal 11 (Scheme 3) in 4 steps and 49% overall yield. The preparations of D-tagatose 1,6-diphosphate and of (3S/4/ )-configurated ketose 1-phosphates by use of aldolases are covered in Chapter 7. 

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